| Arsenic trioxide inhibits osteosarcoma cell invasiveness via MAPK signaling pathway. | |
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MedLine Citation:
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PMID: 20592496 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Arsenic trioxide (As(2)O(3)) is an active ingredient in traditional Chinese medicine. Recent studies showed that it causes apoptosis in several cancer cells. However, research of As(2)O(3) in osteosarcoma is sparse. In our present study, an inhibitory effect of As(2)O(3) on osteosarcoma cell adhesion and metastasis was observed with a cell adhesion, migration and invasion test. The impact of As(2)O(3) on the activities of MMP-9 and MAPK pathway-related downstream factors was analyzed by western blotting. Our results showed that As(2)O(3) significantly inhibited motility, migration and invasion in HOS and MNNG cells in a concentration-dependent manner at concentrations ranging from 0.5-2 μM, and led to cytoskeletal rearrangements. As(2)O(3) exerted an inhibitory effect on the phosphorylation of ERK1/2 and MEK, which are the members of the MAPK family. Additionally, treatment with As(2)O(3) in combination with inhibitors specific for MEK (U0126) in HOS and MNNG cells resulted in a marked inhibition of cell invasion and As(2)O(3) could significantly reduce PMA-induced invasion. In conclusion, we demonstrate the inhibitory effects of As(2)O(3) on the invasiveness of HOS and MNNG cells, which may be due at least partly to inactivation of the MAPK signaling pathway. |
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Authors:
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Ren Tingting; Guo Wei; Peng Changliang; Lu Xinchang; Yang Yi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-07 |
Journal Detail:
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Title: Cancer biology & therapy Volume: 10 ISSN: 1555-8576 ISO Abbreviation: Cancer Biol. Ther. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-11-03 Completed Date: 2011-04-07 Revised Date: 2013-02-05 |
Medline Journal Info:
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Nlm Unique ID: 101137842 Medline TA: Cancer Biol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 251-7 Citation Subset: IM |
Affiliation:
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Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arsenicals / pharmacology* Bone Neoplasms / drug therapy*, enzymology*, pathology Cell Adhesion / drug effects Cell Line, Tumor Cell Movement / drug effects Humans MAP Kinase Signaling System / drug effects* Matrix Metalloproteinase 9 / metabolism Mice Mice, Nude Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors, metabolism Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors, metabolism Osteosarcoma / drug therapy*, enzymology*, pathology Oxides / pharmacology* Phosphorylation / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Arsenicals; 0/Oxides; 1327-53-3/arsenic trioxide; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 3.4.24.35/Matrix Metalloproteinase 9 |
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